Apparatus for Respiration State Gated Brachytherapy

ABSTRACT

During treatment by brachytherapy, radiation passes beyond the target volume and delivers radiation dose to adjacent tissue such as the lungs and, especially in the case of treatment of the left breast, to the heart. The heart is particularly vulnerable to radiation; to minimise the dose it receives in such circumstances, we propose an apparatus for treatment by brachytherapy comprising an X-ray source sized for insertion into a patient, a respiration state monitor, and a control apparatus adapted to receive respiration state information from the respiration state monitor and control the output of the X-ray source; the control apparatus being arranged to operate the X-ray source at a first output level when the respiration state monitor indicates a degree of lung inflation above a first preset threshold and operate the X-ray source at a second and lower output level when the respiration state monitor indicates a degree of lung inflation below a second preset threshold.

FIELD OF THE INVENTION

The present invention relates to brachytherapy.

BACKGROUND ART

Brachytherapy is a form of radiotherapy where a source of ionisingradiation is placed inside or next to the area requiring treatment. Itusually involves placing radionuclides in or close to a target in orderto deliver radiotherapy. These can be injected into the patient and leftin place permanently while the radioactivity decays, or removed aftertreatment is complete.

A variant of this is so-called high dose rate (“HDR”) brachytherapy.This is administered by inserting one or more catheters into the body topre-defined (planned) positions in the body. A radioactive source isthen propelled from a shielded container along to the end of eachcatheter for a predetermined time, and then withdrawn back into theshielded container. While the source is inside the patient, it deliversthe therapeutic dose to the target. This will inevitably also deliver adose to the surrounding tissue.

One particular application of HDR is referred to as “Accelerated PartialBreast Irradiation” (“APBI”) in which a small, single breast tumour issurgically removed together with a “margin” of tissue beyond the tumour,leaving a cavity in the breast. To prevent tumour recurrence caused byany remaining microscopic malignant or pre-malignant cells in the tissuesurrounding this cavity, a course of radiation therapy is applied tothat tissue. In conventional radiation treatment, radiation is appliedby external beam radiotherapy once a day for typically 5-8 weeksfollowing surgery. With APBI using HDR, the treatment regime isaccelerated to (typically) two treatments a day for just five days.

In one type of HDR treatment, a single Iridium-192 (Ir-192) HDR sourceis used to treat the breast. Either during or a few days after surgery,an applicator comprising a catheter surrounded at its distal end by aninflatable balloon is inserted into the cavity in the breast under localanaesthetic, and water is injected to inflate the balloon so that itfits snugly inside the cavity. The most well-known balloon applicator iscalled MammoSite, made by Hologic Corp. At each treatment session an HDRradioactive source is passed from its shielded container down thecentral catheter to specific positions in the balloon for specificperiods of time, governed by the requirements of the treatment plan, todeliver the therapeutic radiation. The source is then completelywithdrawn back into its shielded container. Typically the source is inplace for between 5 and 20 minutes for each treatment session, dependingon the age (and hence radioactivity) of the radionuclide and therequirements of the treatment plan. The inflated applicator remains inplace within the breast until the final treatment session has finished,whereupon it is deflated and removed.

Recently a form of APBI treatment has been developed using a miniatureX-ray tube instead of a radionuclide (the Xoft Axxent system). We willrefer to this as “Electronic HDR” (“E-HDR”). The advantage of using anX-ray tube is that the radiation can be turned off when it is notneeded, so it has considerable safety and convenience factors comparedwith conventional radionuclide based HDR. Xoft Inc and others havedisclosed the concept of varying the tube voltage (and hence the energyspectrum of the emitted x-rays) and/or the current (and hence the doserate) and/or the direction of the x-ray beam in such a way as to shapethe distribution of the therapeutic radiation dose in order to minimisethe dose to unaffected regions or critical organs.

The field of brachytherapy is distinct from that of external beamradiation therapy, which uses linear accelerators to deliver radiationfrom outside the body. In external beam radiation therapy varioustechniques have been developed for directing, collimating and operatingthe treatment beam (usually to turn it on and off) based on the path ofthe beam relative to the target and other regions of the patient, andthe state of the patient including their breathing cycle. The aim ofthese has been to maximise the dose applied to the target region whileminimising the dose to non-target regions and (in particular) tosensitive regions. These techniques include interventional methods whicharrest breathing for certain periods (such as the Elekta ActiveBreathing Coordinator), and free breathing methods which measure lungvolume, target position, or assumed surrogates for these and control thebeam based on acceptance limits (eg the Varian RPM and Brainlab Exactracsystems).

SUMMARY OF THE INVENTION

During APBI treatment, radiation passes beyond the “target volume” anddelivers radiation dose to the lungs and, especially in the case oftreatment of the left breast, to the heart. The heart is particularlyvulnerable to radiation, and cardiac failure caused by radiation and/ordrug therapy is a major cause of death in breast cancer patients whohave survived 10 or more years after treatment for breast cancer.

The quality of x-radiation (i.e. the energy spectrum) produced by aminiature x-ray tube is different from that produced by Ir-192 andtypically has less penetration into tissue. This means that theradiation dose from the x-ray source is more heavily attenuated(absorbed) with distance, so for any particular patient geometry, theheart will receive less radiation dose from APBI using E-HDR than usingHDR. This can be further mitigated in E-HDR by modifying the dose rateand energy when the tube is irradiating towards the heart, but willstill require a compromise between providing a therapeutic dose to thetarget volume that lies between the tube and the heart and minimisingunwanted dose to the heart.

Example treatment plans have been published showing how the physicaldose to the heart is considerably reduced with E-HDR compared to HDR.However, there is an additional radiobiological factor that worksagainst E-HDR. The radiobiological effectiveness (“RBE”) of x-radiationunder typical clinical treatment conditions is reported to be higherthan that of Ir-192. This means that a particular physical dose from theE-HDR will have greater biological effect than the same physical dosefrom HDR with Ir-192. So although the heart receives a lower physicaldose from E-HDR due to the lesser penetration, the dose that it doesreceive will have a more serious effect on the heart than the equivalentdose delivered by Ir-192. Accordingly, the dose reduction of E-HDRcompared to Ir-192 needs to be very significant if benefits are to berealised.

The present invention therefore provides an apparatus for treatment bybrachytherapy comprising an X-ray source sized for insertion into apatient, a respiration state monitor, and a control apparatus adapted toreceive respiration state information from the respiration state monitorand control the output of the X-ray source; the control apparatus beingarranged to operate the X-ray source at a first output level when therespiration state monitor indicates a degree of lung inflation above afirst preset threshold and operate the X-ray source at a second andlower output level when the respiration state monitor indicates a degreeof lung inflation below a second preset threshold.

The principle is to activate the source only when it is apparent fromthe respiration state that the distance between the source and the heartis near its maximum. In this way, the dose received by the heart isminimised. The control apparatus can thus be arranged to deactivate orsubstantially inhibit the x-ray source when the respiration stateinformation indicates that the patient's heart is less than a pre-setdistance from the source.

The X-ray source can comprise an x-ray tube, in which case the controlapparatus is preferably arranged to gate the tube current to a signalderived from the respiration state monitor.

The respiration state monitor can comprise at least one of an externalrespiration surrogate, an internal marker of heart position, an internalmarker of source position, a direct measure of lung volume, an indirectmeasure of lung volume, or a breath hold prompt.

For simplicity, the first and second thresholds can be the same,although more complex modulation of the output of the x-ray source ispossible. The second output level is preferably zero, although asufficiently low output should be effective in reducing the dose to theheart to an acceptable level.

In another aspect, the present invention provides an apparatus fortreatment by brachytherapy comprising an X-ray source sized forinsertion into a patient, a breath hold prompt, and a control apparatusadapted to control the breath hold prompt and the output of the X-raysource, by activating the X-ray source only when the breath hold promptis active.

BRIEF DESCRIPTION OF THE DRAWINGS

An embodiment of the present invention will now be described by way ofexample, with reference to the accompanying figures in which;

FIG. 1 shows a transverse section through a patient illustrating therelative position of the heart, the lung, and a tumour site at anexhalation point of the respiratory cycle;

FIG. 2 shows a transverse section through a patient illustrating therelative position of the heart, the lung, and a tumour site at aninhalation point of the respiratory cycle;

FIG. 3 shows an idealised respiratory cycle; and

FIG. 4 shows apparatus for delivering an E-HDR source.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The invention exploits the following facts/features to reduce theradiation dose to the heart:

-   -   a) E-HDR dose rate falls off rapidly with distance    -   b) E-HDR radiation can be turned on and off quickly    -   c) The heart is moved away from the left breast when a patient        inhales

By only turning on the radiation beam when the heart is near its maximumdistance from the radiation source, the radiation to the heart will befurther minimised. This is shown in FIGS. 1 and 2, which show a sectionthrough a patient 10 in the exhaled and inhaled state respectively. Theright lung 12 and the left lung 14 are visible, as is the heart 18 and avolume 16 from which a tumour has been surgically removed leaving avoid. Also shown in FIGS. 1 and 2 are the 5% dose levels for an x-raysource located in the volume 16; these cover the target volume for theradiation, i.e. the breast tissue surrounding volume 16. It can be seenthat in the exhaled state shown in FIG. 1, this overlaps with the heart18 whereas in the inhaled state shown in FIG. 2 the heart lies outsidethis range and is therefore subjected to a lesser dose.

This means that the relatively fast switching of an E-HDR source can beused as shown in FIG. 3. An idealised respiration cycle 20 is depicted,in which the degree of lung filling (shown on the Y axis 22) varies withtime along the x axis 24. The respiration cycle of a patient can bemeasured or controlled in a variety of ways that will be apparent tothose skilled in the art. Assuming that the cycle is not manipulated butis allowed to continue uninterrupted, by setting a threshold level 26 itis possible to create a signal indicating when the lung filling isgreater than a certain degree. As is apparent from FIGS. 1 and 2, thiscorrelates generally to a maximum separation of the heart and the targetvolume. This can then be used in E-HDR by gating the tube current (andhence the radiation) to such a signal.

Generally, the signal is required to indicate when the heart is morethan a pre-set distance from the source. Thus, other forms of usefulsignal may include measurements via an external surrogate or an internalmarker of the heart and/or source position itself, or by a direct orindirect measure of lung volume. Alternatively, a breath hold (assistedor otherwise) can be employed, and the tube current gated to the breathhold prompt or to a breath hold report.

FIG. 4 illustrates apparatus embodying the invention. A miniature x-raytube 50 is supplied with current (etc) via a flexible cable 52 whichleads back to a control unit 54. The x-ray tube is insertable into animplant 56; this comprises an inflatable balloon 58 around the end of acatheter 60, the other end 62 of which is open to allow entry of thex-ray tube 50. A concentric outer sleeve 64 is provided outside thecatheter 60 and communicates with the interior of the balloon 58. Thissleeve extends from the balloon 58 to a tap 66 part-way along thecatheter 60 with a valve 68 via which a fluid can be injected orwithdrawn in order to inflate or deflate the balloon 58.

Thus, following removal of a tumour from the volume 16, the catheter canbe inserted until the deflated balloon is within the void left at thetumour site, and a fluid such as water injected via the valve 68 toinflate the balloon 58 and occupy the void. The x-ray tube 50 can thenbe inserted along the catheter 60, pushed via the cable 52 until it liesat one or more predefined treatment positions within the end region ofthe catheter inside the void. The x-ray tube can then be activated bythe control unit 54.

A respiration state monitor is generally depicted as item 70. Asindicated above, this can be a simple breath hold prompt which indicatesto the patient that they should hold their breath in; in this case thecontrol unit 54 will activate the breath hold prompt, activate the x-raytube 50 for a preset period, de-activate the x-ray tube 50, thende-activate the breath hold prompt, and allow the patient to breathagain before repeating the process as required.

Alternatively, the respiration state monitor 70 can be an active devicetaking information from the patient as to their respiration state andfeeding this back to the control unit 54, which will then activate andde-activate the x-ray tube 50 as required in order to correlate doseswith periods of lung inflation.

Generally, the respiration state monitor 70 can be according to any ofthe arrangements disclosed herein, or otherwise, such as to permit thecontrol unit 54 to activate and de-activate the x-ray tube 50 insubstantial synchrony with periods of the respiratory cycle in which thedistance between the heart or other sensitive organs and the irradiationsite is maximised.

The use of breath hold or gating to maximize the distance of the heartfrom the left breast is novel in the context of brachytherapy. It wouldbe difficult to achieve this using conventional HDR because of the needto stop and restart irradiation repeatedly in a short timescale.Inserting and removing the source breath-by-breath would be technicallydifficult, would increase the likelihood of equipment failure, and wouldexpose the tissue surrounding the entrance/exit route to extra radiationdose. It would also be difficult to apply adequate shielding to coverand expose the source in-situ between breaths; such shielding would bebulky, heavy and impractical.

This technique, i.e. for increasing the distance between source tonormal tissue for a radiation source inside the body which can beswitched on and off, is not restricted to treatments of the breast, norto just protecting the heart. For example, the techniques could be usedto reduce dose to the spinal cord or the heart when a miniature x-raytube is introduced into the lung, or during treatment of the vessels ofthe heart (for example for treatment of hyperplasia) in order to spareother organs.

In the above discussion, we describe the de-activation of the x-ray tubewhen lung inflation is below a certain threshold. Although this is thepreferred option, an alternative method would be to reduce the dose rateand/or the energy from the x-ray tube, rather than de-activate itcompletely, when lung inflation is below the threshold. This wouldreduce the dose applied to regions such as the heart to levels that maybe considered acceptable.

It will of course be understood that many variations may be made to theabove-described embodiment without departing from the scope of thepresent invention.

1. Apparatus for treatment by brachytherapy comprising an X-ray sourcesized for insertion into a patient, a respiration state monitor, and acontrol apparatus adapted to receive respiration state information fromthe respiration state monitor and control the output of the X-raysource; the control apparatus being arranged to operate the X-ray sourceat a first output level when the respiration state monitor indicates adegree of lung inflation above a first preset threshold and operate theX-ray source at a second and lower output level when the respirationstate monitor indicates a degree of lung inflation below a second presetthreshold.
 2. Apparatus according to claim 1 in which the X-ray sourcecomprises an X-ray tube.
 3. Apparatus according to claim 2 in which thecontrol apparatus is arranged to gate the tube current to a signalderived from the respiration state monitor.
 4. Apparatus according toclaim 1 in which the control apparatus deactivates the X-ray source whenthe respiration state information indicates that the patient's heart ismore than a pre-set distance from the source.
 5. Apparatus according toclaim 1 in which the respiration state monitor comprises at least oneselected from the list consisting of an external respiration surrogate,an internal marker of heart position, an internal marker of sourceposition, a direct measure of lung volume, an indirect measure of lungvolume, and a breath hold prompt.
 6. Apparatus according to claim 1 inwhich the first and the second preset thresholds are the same. 7.Apparatus according to claim 1 in which the second output level issubstantially zero.
 8. Apparatus for treatment by brachytherapycomprising an X-ray source sized for insertion into a patient, a breathhold prompt, and a control apparatus adapted to control the breath holdprompt and the output of the X-ray source, by activating the X-raysource only when the breath hold prompt is active.